{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:21:36Z","timestamp":1773886896733,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sao Paulo Research Foundation","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Sao Paulo Research Foundation","award":["2013\/07607-8"],"award-info":[{"award-number":["2013\/07607-8"]}]},{"name":"Sao Paulo Research Foundation","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil (CAPES)\u2014Financing","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil (CAPES)\u2014Financing","award":["2013\/07607-8"],"award-info":[{"award-number":["2013\/07607-8"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil (CAPES)\u2014Financing","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"CEPID\u2014FAPESP\u2014OCRC\u2014Obesity and Comorbidities Research Center, Brazil","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"CEPID\u2014FAPESP\u2014OCRC\u2014Obesity and Comorbidities Research Center, Brazil","award":["2013\/07607-8"],"award-info":[{"award-number":["2013\/07607-8"]}]},{"name":"CEPID\u2014FAPESP\u2014OCRC\u2014Obesity and Comorbidities Research Center, Brazil","award":["2019"],"award-info":[{"award-number":["2019"]}]},{"name":"Nebraska DHHS Stem Cell","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Nebraska DHHS Stem Cell","award":["2013\/07607-8"],"award-info":[{"award-number":["2013\/07607-8"]}]},{"name":"Nebraska DHHS Stem Cell","award":["2019"],"award-info":[{"award-number":["2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Because of the interface between coagulation and the immune response, it is expected that COVID-19-associated coagulopathy occurs via activated protein C signaling. The objective was to explore putative changes in the expression of the protein C signaling network in the liver, peripheral blood mononuclear cells, and nasal epithelium of patients with COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the COVID-19 Cell Atlas database. A functional protein\u2013protein interaction network was constructed for the protein C gene. Patients with COVID-19 showed downregulation of protein C and components of the downstream protein C signaling cascade. The percentage of hepatocytes expressing protein C was lower. Part of the liver cell clusters expressing protein C presented increased expression of ACE2. In PBMC, there was increased ACE2, inflammatory, and pro-coagulation transcripts. In the nasal epithelium, PROC, ACE2, and PROS1 were expressed by the ciliated cell cluster, revealing co-expression of ACE-2 with transcripts encoding proteins belonging to the coagulation and immune system interface. Finally, there was upregulation of coagulation factor 3 transcript in the liver and PBMC. Protein C could play a mechanistic role in the hypercoagulability syndrome affecting patients with severe COVID-19.<\/jats:p>","DOI":"10.3390\/v14122753","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T03:36:09Z","timestamp":1670816169000},"page":"2753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Downregulation of the Protein C Signaling System Is Associated with COVID-19 Hypercoagulability\u2014A Single-Cell Transcriptomics Analysis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1555-7648","authenticated-orcid":false,"given":"Bruna Rafaela Santos","family":"Silva","sequence":"first","affiliation":[{"name":"Nursing School, University of Campinas, Tessalia Vieira de Camargo, 126, Campinas 13084-970, Brazil"},{"name":"Laboratory of Cell Signalling, Obesity and Comorbidities Center, OCRC, University of Campinas, Carl Von Linnaeus, s\/n, Campinas 13084-864, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Poblete","family":"Jara","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE 68588-0643, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davi","family":"Sidarta-Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signalling, Obesity and Comorbidities Center, OCRC, University of Campinas, Carl Von Linnaeus, s\/n, Campinas 13084-864, Brazil"},{"name":"School of Medical Sciences, University of Campinas, Tessalia Vieira de Camargo, 126, Campinas 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Licio A.","family":"Velloso","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signalling, Obesity and Comorbidities Center, OCRC, University of Campinas, Carl Von Linnaeus, s\/n, Campinas 13084-864, Brazil"},{"name":"School of Medical Sciences, University of Campinas, Tessalia Vieira de Camargo, 126, Campinas 13083-887, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William H.","family":"Velander","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE 68588-0643, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliana P.","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Nursing School, University of Campinas, Tessalia Vieira de Camargo, 126, Campinas 13084-970, Brazil"},{"name":"Laboratory of Cell Signalling, Obesity and Comorbidities Center, OCRC, University of Campinas, Carl Von Linnaeus, s\/n, Campinas 13084-864, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Iba, T., Warkentin, T.E., Thachil, J., Levi, M., and Levy, J.H. 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